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dc.contributor.author
Cayrol, Maria Florencia
dc.contributor.author
Praditsuktavorn, Pannee
dc.contributor.author
Fernando, Tharu M.
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Kwiatkowski, Nicholas
dc.contributor.author
Marullo, Rosella
dc.contributor.author
Calvo Vidal, M. Nieves
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Phillip, Jude
dc.contributor.author
Pera, Benet
dc.contributor.author
Yang, Shao Ning
dc.contributor.author
Takpradit, Kaipol
dc.contributor.author
Roman, Lidia
dc.contributor.author
Gaudiano, Marcello
dc.contributor.author
Crescenzo, Ramona
dc.contributor.author
Ruan, Jia
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Inghirami, Giorgio
dc.contributor.author
Zhang, Tinghu
dc.contributor.author
Cremaschi, Graciela Alicia
dc.contributor.author
Gray, Nathanael S.
dc.contributor.author
Cerchietti, Leandro
dc.date.available
2018-08-16T18:07:25Z
dc.date.issued
2017-01
dc.identifier.citation
Cayrol, Maria Florencia; Praditsuktavorn, Pannee; Fernando, Tharu M.; Kwiatkowski, Nicholas; Marullo, Rosella; et al.; THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors; Nature; Nature Communications; 8; 1-2017; 1-11
dc.identifier.issn
2041-1723
dc.identifier.uri
http://hdl.handle.net/11336/55957
dc.description.abstract
Peripheral T-cell lymphomas (PTCL) are aggressive diseases with poor response to chemotherapy and dismal survival. Identification of effective strategies to target PTCL biology represents an urgent need. Here we report that PTCL are sensitive to transcription-targeting drugs, and, in particular, to THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7). The STAT-signalling pathway is highly vulnerable to THZ1 even in PTCL cells that carry the activating STAT3 mutation Y640F. In mutant cells, CDK7 inhibition decreases STAT3 chromatin binding and expression of highly transcribed target genes like MYC, PIM1, MCL1, CD30, IL2RA, CDC25A and IL4R. In surviving cells, THZ1 decreases the expression of STAT-regulated anti-apoptotic BH3 family members MCL1 and BCL-XL sensitizing PTCL cells to BH3 mimetic drugs. Accordingly, the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nature
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
Cdk7
dc.subject
Bcl2
dc.subject
T Cell Lymphoma
dc.subject.classification
Otras Medicina Básica
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-06T19:42:52Z
dc.journal.volume
8
dc.journal.pagination
1-11
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: Cayrol, Maria Florencia. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Cornell University; Estados Unidos
dc.description.fil
Fil: Praditsuktavorn, Pannee. Cornell University; Estados Unidos
dc.description.fil
Fil: Fernando, Tharu M.. Cornell University; Estados Unidos
dc.description.fil
Fil: Kwiatkowski, Nicholas. Harvard Medical School; Estados Unidos
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Fil: Marullo, Rosella. Cornell University; Estados Unidos
dc.description.fil
Fil: Calvo Vidal, M. Nieves. Cornell University; Estados Unidos
dc.description.fil
Fil: Phillip, Jude. Cornell University; Estados Unidos
dc.description.fil
Fil: Pera, Benet. Cornell University; Estados Unidos
dc.description.fil
Fil: Yang, Shao Ning. Cornell University; Estados Unidos
dc.description.fil
Fil: Takpradit, Kaipol. Cornell University; Estados Unidos
dc.description.fil
Fil: Roman, Lidia. Cornell University; Estados Unidos
dc.description.fil
Fil: Gaudiano, Marcello. Cornell University; Estados Unidos
dc.description.fil
Fil: Crescenzo, Ramona. Cornell University; Estados Unidos
dc.description.fil
Fil: Ruan, Jia. Cornell University; Estados Unidos
dc.description.fil
Fil: Inghirami, Giorgio. Cornell University; Estados Unidos
dc.description.fil
Fil: Zhang, Tinghu. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Cremaschi, Graciela Alicia. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
dc.description.fil
Fil: Gray, Nathanael S.. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Cerchietti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Cornell University; Estados Unidos
dc.journal.title
Nature Communications
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/ncomms14290
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/ncomms14290
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